A multicenter, randomized, double-blind, active-controlled, parallel group, 2-arm study to investigate the effect of estradiol valerate/dienogest compared to Microgynon on hormone withdrawal associated symptoms in otherwise healthy women after 6 cycles of treatment

INTERVENTION: Product Name: SH T00658ID Product Code: SH T 00658 EA Pharmaceutical Form: Capsule* INN or Proposed INN: ESTRADIOL VALERATE CAS Number: 979328 Current Sponsor code: ZK 5104 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 3‐ Product Name: SH T00658ID Product Code: SH T 00658 GA Pharmaceutical Form: Capsule* INN or Proposed INN: ESTRADIOL VALERATE CAS Number: 979328 Current Sponsor code: ZK 5104 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2‐ INN or Proposed INN: DIENOGEST CAS Number: 65928587 Current Sponsor code: ZK 37659 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2‐ Product Name: SH T00658ID Product Code: SH T 00658 M Pharmaceutical Form: Capsule* INN or Proposed INN: ESTRADIOL VALERATE CAS Number: 979328 Current Sponsor code: ZK 5104 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2‐ INN or Proposed INN: DIENOGEST CAS Number: 65928587 Current Sponsor code: ZK 37659 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 3‐ Product Name: SH T00658ID Product Code: SH T 00658 HA Pharmaceutical Form: Capsule* INN or Proposed INN: ESTRADIOL VALERATE CAS Number: 979328 Current Sponsor code: ZK 5104 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1‐ Trade Name: Microgynon 30 ED Product Name: Microgynon 30 Product Code: SH 1155A Pharmaceutical Form: Capsule* INN or Proposed INN: ETHINYLESTRADIOL CAS Number: 57‐63‐6 Current Sponsor code: ZK 4944 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.03‐ INN or Proposed INN: LEVONORGESTREL CAS Number: 797637 Current Sponsor code: ZK 18206 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 0.15‐ CONDITION: Hormone withdrawal associated symptoms of headache and pelvic pain suffered by patients receiving LNG containing oral contraception. ; MedDRA version: 9.1 Level: LLT Classification code 10030970 Term: Oral contraception PRIMARY OUTCOME: Main Objective: To show superiority to Microgynon with regard to the change in the average of the 3 highest VAS values of the hormone withdrawal associated symptoms headache and pelvic pain on cycle days 22‐28 from baseline to cycle 6 in approximately 440 women Primary end point(s): The primary efficacy variable is the individual change of pelvic pain (stratum 1) or the individual change of headache (stratum 2) as determined by the change of average of the 3 highest VAS values during cycle days 22 to 28 from baseline to cycle 6. Secondary Objective: The secondary objectives of this study are to show superiority to Microgynon with regard to; • rescue medication consumption, baseline to cycle 6; • frequency and intensity of other hormone‐related symptoms (bloating or swelling, breast tenderness, and nausea or vomiting) during cycle days 22 to 28, baseline to cycle 6; • prevalence of individual hormone‐related symptoms during cycle days 1 to 21, baseline to cycle 6; • prevalence of individual hormone‐related symptoms during hormone‐free interval, i.e. cycle days 27+28 for EV/DNG capsules and cycle days 22 to 28 for the comparator; • change in the average of the 3 highest VAS values of the hormone withdrawal associated symptoms pelvic pain or headache during cycle days 22 to 28 from baseline to cycle 3; • bleeding pattern and cycle control ; • QoL Questionnaires: Psychological General Well‐Being Index (PGWBI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q‐LES‐Q) and Clinical Global Index (CGI). INCLUSION CRITERIA: 1. Signed and dated informed consent 2. Age between 18 and 50 years (inclusive) at visit 1, for smokers up to 35 years (inclusive) 3. Otherwise healthy female subjects requesting contraception and currently using an LNG, GSD or DSG containing OC in a 21‐day regimen for at least 3 cycles before visit 1 and suffering from at least moderate pelvic pain, headache or both defined by an average value of = 35 mm for the 3 highest VAS values during cycle days 22‐28. 4. Normal or clinically insignificant cervical smear not requiring further follow‐up (a cervical smear has to be taken at the screening visit or a normal result has to be documented that was obtained within the last 6 months before screening). Subjects with atypic squamous or glandular cells of undetermined significance (ASCUS) can be included if they have a negative human papilloma virus (HPV) test result. 5. Able to tolerate ibuprofen and willing to use only ibuprofen supplied for the study.<